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Polymorphisms in the apolipoprotein B-100 gene contributes to normal variation in plasma lipids in 464 Danish men born in 1948

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Abstract

We have studied the possible association of 5 polymorphisms in the apoB gene [a 9-bp insertion/deletion length polymorphism in the signal peptide coding region, XbaI, MspI, and EcoRI restriction fragment length polymorphisms (RFLPs) and a 15-bp variable number of tandem repeats (VNTR) region 3′ to the apoB gene] with plasma concentrations of cholesterol, high density lipoprotein cholesterol, triglycerides and apolipoprotein B-100 in 464 randomly selected Danish men born in 1948. The XbaI RFLP and the insertion/deletion length polymorphism were significantly associated with plasma concentration and inter-individual variation of cholesterol and apolipoprotein B-100 (1.77% and 1.37% of sample variance in cholesterol, and 1.4% and 1.39% of sample variance in apoB). The association was particularly strong in men with a body mass index less than 25 kg/m2 (the mean value of the whole cohort) (3.43% and 2.93% of sample variance in cholesterol, and 3.1% and 2.13% of sample variance in apoB). The XbaI RFLP and the insertion/deletion length polymorphism were in strong linkage disequilibrium, explaining why independent associations of these two polymorphisms with cholesterol and apoB could not be established. There were no other associations between apoB gene polymorphisms and lipoprotein components.

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References

  • Berg K (1986) DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level. Clin Genet 30:515–520

    Google Scholar 

  • Berg K, Hames C, Dahlen G, Frick MH, Krishan I (1976) Genetic variation in serum low density lipoproteins and lipid levels in man. Proc Natl Acad Sci USA 3:937–940

    Google Scholar 

  • Berg K, Powell LM, Wallis SC, Pease R, Knott TJ, Scott J (1986) Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: assignment of the Ag locus. Proc Natl Acad Sci USA 83:7367–7370

    Google Scholar 

  • Boerwinkle E, Xiong W, Fourest E, Chan L (1989) Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: application to the apolipoprotein B 3′-hypervariable region. Proc Natl Acad Sci USA 86:212–216

    Google Scholar 

  • Boerwinkle E, Lee SS, Butler R, Schumaker VN, Chan L (1990) Rapid typing of apolipoprotein B DNA polymorphisms by DNA amplification. Atherosclerosis 81:225–232

    Google Scholar 

  • Bütler R (1990) The Ag-system, a genetic polymorphism of human low density lipoprotein, and its application in forensic serology. In: Lee HC, Gaensslen RE (eds) Advances in forensic science, vol 3. Mosby Yearbook, Chicago, pp 135–159

    Google Scholar 

  • Chakravarti A, Elbein SC, Permutt MA (1986) Evidence for increased recombination near the human insulin gene: implication for disease association studies. Proc Natl Acad Sci USA 83:1045–1049

    Google Scholar 

  • Chen S-H, Yang C-Y, Chen P-F, Setzer D, Tanimura M, Li W-H, Gotto AM Jr, Chan L (1986) The complete cDNA and amino acid sequence of human apo-lipoprotein B-100. J Biol Chem 28:12918–12921

    Google Scholar 

  • Darnfors C, Wiklund O, Nilsson J, Gerard B, Carlsson P, Johansson S, Bondjers G, Bjurseel G (1989) Lack of correlation between the apolipoprotein B XbaI polymorphism and blood lipid levels in a Swedish population. Atherosclerosis 75:183–188

    Google Scholar 

  • Durrington PN, Hunt L, Ishola M, Kane J, Stepehns WP (1986) Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction. Br Heart J 56:206–212

    Google Scholar 

  • Foster DM, Chait A, Albers JJ, Failor RA, Harris C, Brunzell JD (1986) Evidence for kinetic heterogeneity among human low density lipoproteins. Metabolism 8:685–696

    Google Scholar 

  • Friedl W, Ludwig EH, Paulweber B, Sandhofer F, McCarthy BJ (1990) Hypervariability in a minisatellite 3′ of the apolipoprotein B gene in patients with coronary heart disease compared with normal controls. J Lipid Res 31:659–665

    Google Scholar 

  • Gerdes LU, Klausen IC, Faergeman O (1990) The effect of BMI and apoE phenotypes on lipid levels in 477 Danish men born in 1948. Proceedings from the 55th Meeting of the European Atherosclerosis Society, Brügge, p 37

  • Goldstein JL, Brown MS (1983) Familial hypercholesterolemia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 672–712

    Google Scholar 

  • Hansen PS, Rüdiger N, Tybjærg-Hansen A, Færgeman O, Gregersen N (1991) Detection of the apoB-3500 mutation by gene amplification and cleavage with MspI. J Lipid Res 32:1229–1233

    Google Scholar 

  • Hegele RA, Huang L-S, Blum CB, Buring JE, Breslow JL (1986) Apolipoprotein B-gene DNA polymorphisms associated with myocardial infarction. N Engl J Med 24:1509–1515

    Google Scholar 

  • Hill WG (1974) Estimation of linkage disequilibrium in randomly mating populations. Heredity 33:229–239

    Google Scholar 

  • Houlston RS, Turner PR, Lewis B, Humphries SE (1990) Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics. Gen Epidemiol 7:199–210

    Google Scholar 

  • Knott TJ, Pease RJ, Powell LM, Wallis SC, Rall SC, Innerarity TL, Blackhart B, Taylor WH, Marcel Y, Milne R, Johnson D, Fuller M, Lusis AJ, McCarthy BJ, Mahley RW, Levy-Wilson B, Scott J (1986) Complete protein sequence and identification of structural domains of human apolipoprotein B. Nature 323:734–738

    Google Scholar 

  • Law A, Powell LM, Brunt H, Knott TJ, Altman DG, Rajput J, Wallis SC, Pease RJ, Priestley LM, Scott J, Miller GJ, Miller NE (1986) Common DNA polymorphism within coding sequence of apolipoprotein B gene associated with altered lipid levels. Lancet I:1301–1303

    Google Scholar 

  • Myklebost O, Rogne S, Hjermann I, Olaisen B, Prydz H (1990) Association analysis of lipid levels and apolipoprotein restriction fragment length polymorphisms. Hum Genet 86:209–214

    Google Scholar 

  • Paulweber B, Friedl W, Krempler F, Humphries SE, Sandhofer F (1990) Association of DNA polymorphism at the apolipoprotein B gene locus with coronary heart disease and serum very low density lipoprotein levels. Arteriosclerosis 10:17–24

    Google Scholar 

  • Priestley L, Knott T, Wallis S, Powell L, Pease R, Simon A, Scott J (1985) RFLP for the human apolipoprotein B aene: I–V. Nucleic Acids Res 18:6789

    Google Scholar 

  • Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37:268–285

    CAS  PubMed  Google Scholar 

  • Sing CF, Orr JD (1978) Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan. IV. Separation of polygene from common environmental effects. Am J Hum Genet 30:491–504

    Google Scholar 

  • Sniderman A, Shapiro S, Marpole D, Malcolm I, Skinner B, Kwiterovich PO Jr (1980) Association of coronary atherosclerosis with hyperapobetalipoproteinemia (increased protein but normal cholesterol content in human plasma low density lipoprotein). Proc Natl Acad Sci USA 77:604–608

    Google Scholar 

  • Soria LF, Ludwig EH, Clarke HRG, Vega GL, Grundy SM, Mc-Carthy BJ (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 86:587–591

    Google Scholar 

  • Talmud PJ, Barni N, Kessling AM, Carlsson P, Darnfors C, Bjursell G, Galton D, Wynn V, Kirk H, Hayden MR, Humphries SE (1987) Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normoand hyperlipidaemic individuals. Atherosclerosis 67:81–89

    Google Scholar 

  • Thompson EA, Deeb S, Walkers D, Motulsky AG (1988) The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet 42:113–124

    Google Scholar 

  • Tybjærg-Hansen A, Nordestgaard BG, Gerdes LU, Humphries SE (1991) Variation of apolipoprotein B gene is associated with myocardial infarction and lipoprotein levels in Danes. Atherosclerosis 89:69–81

    Google Scholar 

  • Vogel F, Motulsky AG (1986) Human genetics: problems and approaches, 2nd edn. Springer, Berlin Heidelberg New York Tokyo, pp 642–644

    Google Scholar 

  • Whayne TF, Alaupovic P, Curry MD, Lee ET, Anderson PS, Schechter E (1981) Plasma apolipoprotein B and VLDL-, LDL-, and HDL-cholesterol as risk factors in the development of coronary artery disease in male patients examined by angiography. Atherosclerosis 39:411–424

    Google Scholar 

  • Xu C-F, Tikkanen MJ, Huttunen JK, Pietinen P, Bütler R, Humphries S, Talmud P (1990) Apolipoprotein B signal peptide insertion/ deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels. J Lipid Res 31:1255–1261

    Google Scholar 

  • Yang C-Y, Chen S-H, Gianturco SH, Bradley WA, Sparrow JT, Tanimura M, Li W-H, Sparrow DA, DeLoof H, Rosseneu M, Lee F-S Gu Z-W, Gotto AM Jr, Chan L (1986) Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100. Nature 323:738–740

    Google Scholar 

  • Young SG (1990) Recent progress in understanding apolipoprotein B. Circulation 82:1574–1594

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Tage-Hansensgade 2, DK-8000, Aarhus C, Denmark

    Peter Steen Hansen, Lars Ulrik Gerdes, I. C. Klausen & Ole Faergeman

  2. Molecular-Genetic Laboratory, Department of Clinical Chemistry, Skejby Sygehus and Aarhus Kommunehospital University Hospital, University of Aarhus, DK-8000, Aarhus C, Denmark

    Niels Gregersen

Authors
  1. Peter Steen Hansen
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  2. Lars Ulrik Gerdes
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  3. I. C. Klausen
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  4. Niels Gregersen
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  5. Ole Faergeman
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Hansen, P.S., Gerdes, L.U., Klausen, I.C. et al. Polymorphisms in the apolipoprotein B-100 gene contributes to normal variation in plasma lipids in 464 Danish men born in 1948. Hum Genet 91, 45–50 (1993). https://doi.org/10.1007/BF00230221

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  • DOI: https://doi.org/10.1007/BF00230221

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